Diagnostic dilemma between angular and interstitial ectopic pregnancy: 3D ultrasound features.

Angular pregnancy is a rare entity which is commonly confused with interstitial or cornual pregnancies. A lack of consensus about the specific ultrasound features of these 3 entities leads to inappropriate interchange between them among the literature. An angular pregnancy should be considered as a potentially viable intra-uterine eccentric pregnancy as it might be carried to term and result in a live-born baby whereas interstitial or cornual pregnancies should be considered as ectopic pregnancies which should be interrupted. We report here two cases of women at 8 weeks of pregnancy with an angular pregnancy diagnosed by vaginal 2D and 3D ultrasound and discuss about specific ultrasound features and alternative imaging modalities to distinguish it from interstitial and cornual pregnancies.

Prenatal diagnosis of rhombencephalosynapsis: neuroimaging features and severity of vermian anomaly.

OBJECTIVES: To describe the prenatal neuroimaging spectrum of rhombencephalosynapsis (RES) and criteria for its classification according to the severity of vermian anomaly. METHODS: In this multicenter retrospective study of fetuses with RES between 2002 and 2020, the medical records and brain ultrasound and magnetic resonance images were evaluated comprehensively to determine the severity of the vermian anomaly and the presence of associated brain findings. RES was classified, according to the pattern of vermian agenesis and the extent of the fusion of the hemispheres, as complete RES (complete absence of the vermis) or partial RES (further classified according to the part of the vermis that was missing and, consequently, the region of hemispheric fusion, as anterior, posterior, severe or mixed RES). Findings were compared between cases with complete and those with partial RES. RESULTS: Included in the study were 62 fetuses with a gestational age ranging between 12 and 37 weeks. Most had complete absence of the vermis (complete RES, 77.4% of cases), a 'round-shaped' cerebellum on axial views (72.6%) and a transverse cerebellar diameter (TCD) < 3rd centile (87.1%). Among the 22.6% of cases with partial RES, 6.5% were classified as severe partial, 6.5% as partial anterior, 8.1% as partial mixed and 1.6% as partial posterior. Half of these cases presented with normal or nearly normal cerebellar morphology and 28.5% had a TCD within the normal limits. Infratentorially, the fourth ventricle was abnormal in 88.7% of cases overall, and anomalies of the midbrain and pons were frequent (93.5% and 77.4%, respectively). Ventriculomegaly was observed in 80.6% of all cases, being more severe in cases with complete RES than in those with partial RES, with high rates of parenchymal and septal disruption. CONCLUSIONS: This study provides prenatal neuroimaging criteria for the diagnosis and classification of RES, and identification of related features, using ultrasound and magnetic resonance imaging. According to our findings, a diagnosis of RES should be considered in fetuses with a small TCD (severe cerebellar hypoplasia) and/or a round-shaped cerebellum on axial views, during the second or third trimester, especially when associated with ventriculomegaly. Partial RES is more common than previously thought, but presents an extreme diagnostic challenge, especially in cases with normal or nearly-normal cerebellar morphobiometric features. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Imaging of anorectal malformations in utero.

PURPOSE: To document the imaging findings suggestive of anorectal malformation (ARMs) on prenatal US and MRI. METHODS: Retrospective evaluation of the screening US and prenatal MRI exams of the rectum and ano-perineal region in normal fetuses and in patients with ARMs. RESULTS: Examples showing the normal rectal and anoperineal anatomy on prenatal US and MRI exams and the imaging findings observed in different types of confirmed ARMS. CONCLUSIONS: Prenatal diagnosis of ARMs requires both a systematic evaluation of the fetal pelvis and perineum and an appropriate knowledge of its suggestive imaging findings.

Dermatological manifestations in cardiofaciocutaneous syndrome: a prospective multicentric study of 45 mutation-positive patients.

BACKGROUND: Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification. OBJECTIVES: To describe the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype-genotype correlations. METHODS: We performed a 4-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Forty-five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype-genotype correlation was determined. CONCLUSIONS: A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.

Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation.

BACKGROUND: Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited dermatological expertise. OBJECTIVES: To describe the dermatological manifestations of NS, compare them with the literature findings, and test for dermatological phenotype-genotype correlations with or without the presence of PTPN11 mutations. METHODS: We performed a large 4-year, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11-NS, 34 patients with PTPN11-NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11-NS, present in 53·8% of patients. Multiple lentigines and café-au-lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P = 0·001), including keratosis pilaris (P = 0·005), ulerythema ophryogenes (P = 0·0001) and palmar and/or plantar hyperkeratosis (P = 0·06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P = 0·035) and scarce or absent eyelashes (P = 0·06, trend association) than those with PTPN11 mutations. CONCLUSIONS: The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.

INTU-related oral-facial-digital syndrome type VI: A confirmatory report.

Oral-facial-digital (OFD) syndromes are a subgroup of ciliopathies distinguished by the co-occurrence of hamartomas and/or multiple frenula of the oral region and digital anomalies. Several clinical forms of OFD syndromes are distinguished by their associated anomalies and/or inheritance patterns, and at least 20 genetic types of OFD syndromes have been delineated. We describe here a child with preaxial and postaxial polydactyly, lingual hamartoma, a congenital heart defect, delayed development and cerebellar peduncles displaying the molar tooth sign. Whole-exome sequencing and SNP array identified compound heterozygous variants in the INTU gene, which encodes a protein involved in the positioning of the ciliary basal body. INTU is a subunit of the CPLANE multiprotein complex essential for the assembly of IFT-A particles and intraflagellar transport. This report of a second patient with INTU-related OFD syndrome and the further delineation of its neuroimaging and skeletal phenotype now allow INTU-related OFD syndromes to be classified within the OFD syndrome type VI group. Patients display a phenotype similar to that of mice with a hypomorphic mutation of Intu, but with the addition of a heart defect.

Complete Maxillo-Mandibular Syngnathia in a Newborn with Multiple Congenital Malformations.

Syngnathia is an extremely rare condition involving congenital fusion of the maxilla with the mandible. Clinical presentations vary from simple mucosal bands (synechiae) to complete bony fusion (synostosis). Most cases are unilateral incomplete fusions. We report the case of a severely growth-retarded newborn infant with complete synostosis of the mandible with the maxilla and the zygoma associated with cleft palate, choanal atresia, deafness, delayed cerebral white matter development, and genital and limb malformations. Extensive genetic analysis did not reveal any mutations. This association of multiple congenital malformations may represent an entity distinct from previously described syndromes associated with syngnathia.

Intrauterine growth restriction is associated with structural alterations in human umbilical cord and decreased nitric oxide-induced relaxation of umbilical vein.

INTRODUCTION: Intrauterine growth restriction (IUGR) affects ∼8% of all pregnancies and is associated with major perinatal mortality and morbidity, and with an increased risk to develop cardiovascular diseases in adulthood. Despite identification of several risk factors, the mechanisms implicated in the development of IUGR remain poorly understood. In case of placental insufficiency, reduced delivery of oxygen and/or nutrients to the fetus could be associated with alterations in the umbilical circulation, contributing further to the impairment of maternal-fetal exchanges. We compared the structural and functional properties of umbilical cords from growth-restricted and appropriate for gestational age (AGA) term newborns, with particular attention to the umbilical vein (UV). METHODS: Human umbilical cords were collected at delivery. Morphological changes were investigated by histomorphometry, and UV's reactivity by pharmacological studies. RESULTS: Growth-restricted newborns displayed significantly lower growth parameters, placental weight and umbilical cord diameter than AGA controls. Total cross-section and smooth muscle areas were significantly smaller in UV of growth-restricted neonates than in controls. Maximal vasoconstriction achieved in isolated UV was lower in growth-restricted boys than in controls, whereas nitric oxide-induced relaxation was significantly reduced in UV of growth-restricted girls compared to controls. CONCLUSION: IUGR is associated with structural alterations of the UV in both genders, and with a decreased nitric oxide-induced relaxation in UV of newborn girls, whereas boys display impaired vasoconstriction. Further investigations will allow to better understand the regulation of umbilical circulation in growth-restricted neonates, which could contribute to devise potential novel therapeutic strategies to prevent or limit the development of IUGR.

High mobility group box 1 protein (HMGB-1): a pathogenic role in preeclampsia?

We evaluated whether preeclampsia is associated with elevated circulating levels of High mobility group box 1 protein (HMGB-1), a nuclear protein with proinflammatory effects when released extracellularly. We enrolled 48 women, 32 in third trimester pregnancy (16 with, 16 without preeclampsia), and 16 healthy non pregnant. In the peripheral blood of pregnant women, HMGB-1 concentration was assessed serially, before and after delivery. With or without preeclampsia, third trimester pregnancy was associated with elevated levels of HMGB-1. This elevation is exaggerated in preeclampsia. The source of HMGB-1 observed in these conditions is likely to involve tissues other than the placenta itself.

Inexperienced sonographers can successfully visualize and assess a three-dimensional image of the fetal face using a standardized ultrasound protocol.

INTRODUCTION: A standardized three-dimensional ultrasonographic (3DUS) protocol is described that allows fetal face reconstruction. Ability to identify cleft lip with 3DUS using this protocol was assessed by operators with minimal 3DUS experience. MATERIAL AND METHODS: 260 stored volumes of fetal face were analyzed using a standardized protocol by operators with different levels of competence in 3DUS. The outcomes studied were: (1) the performance of post-processing 3D face volumes for the detection of facial clefts; (2) the ability of a resident with minimal 3DUS experience to reconstruct the acquired facial volumes, and (3) the time needed to reconstruct each plane to allow proper diagnosis of a cleft. RESULTS: The three orthogonal planes of the fetal face (axial, sagittal and coronal) were adequately reconstructed with similar performance when acquired by a maternal-fetal medicine specialist or by residents with minimal experience (72 vs. 76%, p = 0.629). The learning curve for manipulation of 3DUS volumes of the fetal face corresponds to 30 cases and is independent of the operator's level of experience. DISCUSSION: The learning curve for the standardized protocol we describe is short, even for inexperienced sonographers. This technique might decrease the length of anatomy ultrasounds and improve the ability to visualize fetal face anomalies.

PP125. High mobility group box 1 protein (HMGB1): A pathogenic role in preeclampsia?

INTRODUCTION: A central pathogenic mechanism of preeclampsia is believed to be the production by the hypoxic placenta of various mediators which promote inflammation and oxidative stress when released into the maternal circulation. The high mobility group box 1 protein (HMGB1) is a ubiquitous nuclear protein. In conditions of hypoxic cellular stress or necrosis, HMGB1 is released into the extracellular milieu. Extracellular HMGB1 has proinflammatory effects, due to the engagement of various cell membrane receptors, notably the receptor for advanced glycation products (RAGE). OBJECTIVES: In preeclampsia, there is evidence for activation of RAGE, and enhanced amounts of HMGB1 have also been demonstrated in the placenta and amniotic fluid, but not, so far, in maternal blood. We hypothesize therefore that, in preeclampsia, the concentration of HMGB1 is abnormally high in maternal blood. METHODS: We enrolled 16 women in third trimester pregnancy and suffering from preeclampsia (blood pressure > 140/90mmHg with significant proteinuria), 16 women with normal pregnancies who were matched pairwise with the former for BMI and gestation week, and 16 non pregnant healthy women, matched for age with the other two groups. HMGB1 was assessed in peripheral blood with a commercial ELISA kit. The variance between the three groups was appreciated using an ANOVA analysis. Significance was considered for a probability value of < 0.5. RESULTS: The median [interquartile range] HMGB1 concentrations (in ng/mL) were 2.1 [1.1-3.2] in preeclamptic pregnancies, 1.1 [1.0-1.2] in normal pregnancies (p<0.05 vs preeclamptic group), and 0.6 [0.5-0.8] in non pregnant women (p<0.01 vs both other groups). CONCLUSION: In third trimester pregnancy, the presence of preeclampsia is associated with an approximately two-fold increase of HMGB1 concentration in maternal peripheral blood. Considering its known proinflammatory effects, HMGB1 could be one mediator responsible for the maternal manifestations of preeclampsia.

[Fast-track multimodal rehabilitation after cesarean, the sum of all tricks]. / Réhabilitation accélérée multimodate postcésarienne, la somme de toutes les astuces.

Fast-track multimodal rehabilitation after cesarean, the sum of all tricks Fast-track multimodal rehabilitation after caesarean is an interdisciplinary concept allowing an accelerated return to normal physiology. Fast-track rehabilitation combines minimising surgical trauma, regional anaesthesia and active management of pain control, minimally invasive postoperative care while promoting return to autonomy.

[Interprofessional collaboration in perinatality: an obstetrical goal]. / Travailler sur les articulations interprofessionnelles en périnatalité: un objectif obstétrical.

In the field of perinatality, development of prenatal diagnosis and neonatal management have been impressive. But these were also associated with the emergence of the increasingly important emotional dimension for parents and professionals. Obstetricians dealing with the difficult breaking of bad news, the uncertainties of prenatal diagnosis and the complex somatic, psychological and social follow-up have to work in a multidisciplinary approach. The securing role of a coherent teamwork is recognised by parents as well as health care providers This article discusses interprofessional relationship as an obstetrical goal and give some landmarks in order to improve the management and the collaboration with parents.

[Hypertension in pregnancy]. / Hypertension et grossesse.

Hypertension in pregnancy Hypertension in pregnancy, whether chronic or recently diagnosed, is always a matter of concern for the general practitioner or the obstetrician. Even if this situation often evolves favorably, and although a "wait and see" attitude may be preferred to an aggressive one in such cases, one should also be aware of how dramatic the outcome may also be. As a matter of fact, what is considered as one of the most frequent complications of pregnancy can run out of control, a possibility which shouldn't be dismissed. In this article, we shall discuss the various strategies for managing this disorder.

Right-sided diaphragmatic eventration: a rare cause of non-immune hydrops fetalis.

We report 2 cases of non-immune hydrops fetalis (NIHF) in which autopsy findings revealed an association with right-sided congenital diaphragmatic eventration (CDE). Both patients born at 30 weeks of gestation presented with severe generalized skin oedema, pleural effusions and ascites. They both died shortly after birth of cardiorespiratory insufficiency due to lung hypoplasia and low output heart failure. The right thoracic cavity was filled with the membranous but intact right diaphragm covering the herniated visceral organs including parts of the liver, small bowel and colon surrounded by voluminous ascites. In similar fashion to the situation seen in congenital diaphragmatic hernia (CDH), the displaced visceral organs led to impaired lung growth resulting in important lung hypoplasia and obstructed venous return. Extravascular liquid accumulation was probably further aggravated by hypoproteinaemia secondary to liver dysfunction resulting from the venous congestion and cardiac failure. In summary, CDE is a rare condition resulting from impaired ingrowth of muscle fibres into the diaphragm during the first trimester. Prenatal differentiation of CDE from CDH is a real challenge. The association of CDE and NIHF has not been previously described.

[Management of in utero foetal death: Which assessment to undertake?]. / Prise en charge de la mort in utero: quel bilan proposer?

OBJECTIVE: To assess the value of para-clinical exams prescribed in case of in utero foetal death, to result in the establishment of a new algorithm of diagnostic tests. MATERIALS AND METHODS: A retrospective analysis on a series of 106 stillbirths gathered between September 1989 and December 1998 in the obstetrical and gynaecological department of the Lausanne University Hospital which is a tertiary centre. Stillbirth was defined as foetal death occurring as from the date of foetal viability. Thus, only pregnancies from 24 weeks and onwards were included in this series. We excluded all stillbirths occurring during medical termination of pregnancy and cases with incomplete data files. The Fretts' classification was used. The different exams asked by the physician were screened and we analysed their pertinence to determine the aetiological diagnosis for each case. The search for significant risk factors was also taken into account. We compared our management of in utero foetal death with data from the literature to propose a new algorithm. RESULTS: The aetiology of in utero foetal death could be attributed in ninety percent of the cases. The principal causes were in utero growth retardation (19.8%), foetal congenital and chromosomal anomalies (18.9%), infections (15.1%), placental abruption (7.5%), preeclampsia (5.6%), maternal diabetes (3.8%). The remaining 18.9% are divided in to miscellaneous causes. In 10.4% of the cases we could not find any explanation to the death of the foetus. The exams that yielded the most information when done were: foetal autopsy which was abnormal in 92.7%, placental investigation which was abnormal in 93% and the babygramme (X-ray of the foetal skeleton) which was abnormal in 53%. Maternal serology for infections was informative in 6.6% of the cases. CONCLUSION: We present here a protocol for the diagnostic management of stillbirth which is differentiated according to the circumstances surrounding the event. This should prove useful to reduce superfluous tests.

Gestational diabetes mellitus and the risk of metabolic syndrome: a population-based study in Lausanne, Switzerland.

AIMS: To investigate the relationships between gestational diabetes mellitus (GDM) and the metabolic syndrome (MS), as it was suggested that insulin resistance was the hallmark of both conditions. To analyse post-partum screening in order to identify risk factors for the subsequent development of type 2 diabetes mellitus (DM). METHODS: A retrospective analysis of all singleton pregnancies diagnosed with GDM at the Lausanne University Hospital for 3 consecutive years. Pre-pregnancy obesity, hypertension and dyslipidaemia were recorded as constituents of the MS. RESULTS: For 5788 deliveries, 159 women (2.7%) with GDM were identified. Constituents of the MS were present before GDM pregnancy in 26% (n = 37/144): 84% (n = 31/37) were obese, 38% (n = 14/37) had hypertension and 22% (n = 8/37) had dyslipidaemia. Gestational hypertension was associated with obesity (OR = 3.2, P = 0.02) and dyslipidaemia (OR = 5.4, P=0.002). Seventy-four women (47%) returned for post-partum OGTT, which was abnormal in 20 women (27%): 11% (n = 8) had type 2 diabetes and 16% (n = 12) had impaired glucose tolerance. Independent predictors of abnormal glucose tolerance in the post-partum were: having > 2 abnormal values on the diagnostic OGTT during pregnancy and presenting MS constituents (OR = 5.2, CI 1.8-23.2 and OR = 5.3, CI 1.3-22.2). CONCLUSIONS: In one fourth of GDM pregnancies, metabolic abnormalities precede the appearance of glucose intolerance. These women have a high risk of developing the MS and type 2 diabetes in later years. Where GDM screening is not universal, practitioners should be aware of those metabolic risks in every pregnant woman presenting with obesity, hypertension or dyslipidaemia, in order to achieve better diagnosis and especially better post-partum follow-up and treatment.

[Pediatrics. Advantages of prenatal diagnosis in congenital cardiopathies]. / Pédiatrie. Avantages du diagnostic prénatal dans les cardiopathies congénitales.

The diagnosis of a congenital heart disease can be made by fetal ultrasound as soon as the 12th week of pregnancy. The main indications for fetal echocardiography are maternal and fetal. Sequential approach is necessary to precise the anatomy and to elaborate a therapeutic strategy for that patient. For severe heart lesions delivery and postnatal care can be programmed, avoiding thus severe hypoxia and acidosis after birth. The prognosis of these children are thus much improved.